e-Bulletin 20

Welcome to the latest edition of the Hepatitis Scotland e-Bulletin.

This bulletin focuses on treatment updates on both Hepatitis B and C as well as considering considering wider health issues important to those affected by viral hepatitis. We also feature some upcoming events. There has been a lot going on in the world of viral hepatitis of late, so we will be producing a second e-bulletin covering more stories very soon.

Tayside in Game Changing Hepatitis C Project

A world leading project using a radical "treatment as prevention" approach is a potentially game changing intervention that may significantly decrease or even eradicate Hepatitis C infections amongst the current and recent injecting drug user population. The ERADICATE Hep C trial was recently launched by the University of Dundee, in partnership with NHS Tayside. It is led by Dr John Dillon, a consultant hepatologist who played a key role in the development of Scotland's internationally recognised Hepatitis C Action Plans.

The £2.2million project is funded by the Scottish Government and pharmaceutical companies Janssen and Roche.

The impact of Hepatitis C on public health and financial cost to the NHS is significant, as well as the impact it has on the health of individuals affected and resultant economic costs, as emphasised by project leader Dr. John Dillon, Clinical Senior Lecturer and Consultant Hepatologist,

““The general thinking in recent times has been that the population of people who inject drugs is generally too unstable and consists of people with lives which are too chaotic to allow for the sort of sustained treatment that Hepatitis C needs to achieve a cure.

“However, our view is that with the right approach, supported with appropriate resources, we can tackle what is a very significant problem and reduce the rates of hepatitis C infection.”

Oxford University research

Dr. Dillon’s assertion that we can tackle Hepatitis C among current injecting drug users to reduce new Hepatitis C infections is backed by research from Greece led by Oxford University (inc University of Athens and Imperial College London). The research shows the increased likelihood of passing on Hepatitis C infection during the early stages of their own illness, potentially due to the high viral load increasing the infectiveness of the virus.. This suggests that early diagnosis and treatment of Hepatitis C in people who inject drugs could prevent many transmissions.

The lead author of the Oxford study, Dr. Gkikas Magiorkinis said, “For the first time we show that super-spreading in Hepatitis C is led by intravenous drug users early in their infection. Using this information we can hopefully soon make a solid argument to support the scaling-up of early diagnosis and antiviral treatment in drug users. Helping these people and stopping the spread of Hepatitis C is our ultimate target.”

Wider burden of Hepatitis C

Reducing Hepatitis C infections and encouraging people to access treatment will not only be of benefit to individuals and indeed to wider public health – but also has an economic benefit.

A research article posted online by BioMed Central Gastroenterology has sought to quantify the health and economic burden of Hepatitis C infection. It surveyed patients from 5 European countries and compared them with non-HCV infected people, also comparing those who had or were receiving treatment with treatment naive patients.

It looked at areas such as Health Related Quality of Life, worker absenteeism, presenteeism (impairment while at work), impairment in non-work related activities and physician visit costs. The research concluded that there is a significant humanistic and economic cost associated with Hepatitis C infection.

However, patterns of results were similar among treatment naive patients, suggesting that Hepatitis C treatment is not driving the higher use of resources and reduced quality of life. As such effective treatment of Hepatitis C infection may relieve work impairment, lower the use of healthcare resources and improve a patients’ quality of life.

A study produced by Rand Europe for the Hepatitis C Trust gave projections of the healthcare and economic burden of Hepatitis C in the UK. Among the key findings were:

Under current treatment patterns, overall prevalence of Hepatitis C infections would increase from 0.44% in 2010 to 0.61% in 2035, a numbers increase of 265,000 to 370,000.

That this rise in prevalence would mean an increase in healthcare costs from £82.7million in 2012 to £115million in 2035. Productivity losses (absenteeism and presenteeism inclusive) were estimated to rise from £184million-£367million in 2010 to £210million-£427million in 2035. (Dependent on assuming minimum wage (lower estimate) or median income (higher estimate) for the productive population.

Quadrupling treatment rates would halt the rise in projected prevalence, with the estimated number of chronically infected individuals falling from 265,000 in 2010 to 262,000 in 2035.

This increase in treatment rates would reduce the number of those with decompensated cirrhosis and hepatocellular carcinoma (liver cancer) from an estimated 17,000 under the current treatment assumption to 12,000 in the increased treatment assumption. These late stage liver diseases often require liver transplant which costs around £100,000.

The average additional cost of antiviral therapy treatment per annum between 2012 and 2035 is estimated at £43.8million. This quadrupling of individuals receiving treatment would lead to a reduction in HCV-related productivity losses of £59m - £122m.

Cumulatively, using the median wage assumption, the average gain in productivity per annum is estimated at £73.3million. With additional treatment costs being estimated at £43.8million this represents a difference of £29.5million, meaning that there would be significant long term financial benefits to quadrupling HCV antiviral therapy.

However.....

The Greek Government has drawn up a list of more than 50 pharmaceutical companies it accuses of either halting or planning to halt supplies of drugs, including for treatment of Hepatitis C. The companies are said to be withholding drugs due to unpaid state debts and due to Greek drug prices being amongst the lowest in Europe, allowing middlemen to export them Europe wide for profit.

Among the companies listed by the government are Pfizer, Roche, Sanofi, GlaxoSmithKline and AstraZeneca. GSK and AstraZeneca have denied the accusation, with the others admitting to some drugs being withheld.

Withholding Hepatitis C antiviral drugs may mean that some people are unable to adhere to their treatment regimen. With Greece experiencing crippling cuts to public health programmes (including needle exchange accompanied by well documented exponential increases in HIV infection) withholding much needed medications appears somewhat unhelpful.

Conclusion

The project in Tayside looks to provide in depth targeted support to those who inject drugs to get onto treatment. This in turn will reduce the number of new HCV infections. Research from Oxford University and Rand demonstrate that there are significant public health benefits to lowering the pool of individuals with HCV infection, and that this is possible even if people are still injecting drugs. There is also the potential for significant savings for the NHS and significant increase in economic output and productivity if we treat more people with Hepatitis C.

Hepatitis B breakthrough

Medical therapy has turned chronic HBV infection into a disease that can often be controlled indefinitely, with enormous benefits to patients. However, the infection is very rarely cleared, so treatment, if needed, can be life-long, expensive, and may be associated with unpredictable long-term side effects.

Researchers from the University of St Louis in the United States have made a breakthrough in research of drugs to combat hepatitis B. Taking advantage of viral similarities with HIV, they were able to measure and block a previously unstudied HBV enzyme (HBV RNAseH) and stop the virus from replicating. This could eventually lead to drugs which can substantially suppress the virus meaning many more patients could clear HBV infection altogether.

Importantly, treatment may not have to completely eradicate the key HBV molecule cccDNA completely, because the latter stages of viral suppression may be assisted by the immune system.

Study author Dr John Travis, Professor of Molecular Biology and Immunology at St Louis University, noted that a cure for Hepatitis B could eliminate many forms of liver cancer worldwide.

Food for thought on diet?

The Academy of Medical Royal Colleges has put forward a 10 point plan aimed at tackling the growing problem of obesity in the UK and to help shed the UKs’ status as fat man of Europe. Key measures they would like to see implemented include a 20% tax on sugary drinks, fewer fast food outlets near schools and a ban on unhealthy food in hospitals. They also suggest that health professionals should routinely ask overweight patients about their lifestyle under the banner of ‘making every contact count’.

The Academy says that the measures they recommend are required to stop ‘generation after generation falling victim to obesity related illnesses and death’, adding that obesity is the greatest public health crisis facing the UK. Obesity related illnesses include heart attack, heart disease, stroke and non alcoholic fatty liver disease.

The 2011 Scottish Health Survey found that just under two thirds (64.3%) of adults over age 16 in Scotland were overweight or obese, with a BMI of 25 or over. Just over a quarter (27.7%) were classed as obese.

Obesity is commonly associated with increased risk for heart disease, heart attacks and strokes. However, obesity is also strongly linked to non alcoholic fatty liver disease. Non alcoholic fatty liver disease (NAFLD) is the term used to describe a wide range of conditions caused by a build up of fat within the liver cells. A healthy liver should contain very little or no fat. NAFLD can potentially be a serious condition because if fat in the liver cells continues to build up it can lead to scarring of the liver. In the worst case it could potentially lead to cirrhosis of the liver – permanent liver scarring which can be fatal. Only a minority of NAFLD patients will develop cirrhosis, but having it can still cause damage to your liver. The disease can affect the liver in much the same way as viral hepatitis.

Therefore if you have hepatitis B or C and are overweight or obese, you could be increasing the progression of serious damage to your liver. For this reason, if you have been diagnosed with hepatitis B or C it is helpful to try to adjust your lifestyle taking into account these factors..

Targeting HCV related mortality, treatment or cause

A recent study investigated the association between chronic liver disease(s) and depression. It found that although depression has been thought to be associated with a number of chronic liver diseases, the association remains strong only for chronic Hepatitis C.

This research may be of particular interest when taken along with a retrospective study from Australia, published in the May 2011 edition of the Journal of Hepatology. This study analysed the specific causes of death among people with chronic hepatitis B and chronic hepatitis C.

Researchers found that cancer rates were significantly higher in those with Hepatitis B compared with those with Hepatitis C with Hepatitis B more likely to lead to primary liver cancer. For HCV infected people the leading cause of death was drug-related, although liver-related deaths were almost as many in number, and the suicide rate was a significant amount in external factors.

The Australian researchers suggested that, based on this, channelling resources into drug addiction treatment programs and suicide prevention may be as equally useful a tool in preventing death in Hepatitis C patients as research into new drug treatments for the virus.

Relevant to these studies is recent piece of research by the Samaritans, in partnership with Network Rail, titled ‘Men and Suicide, why it’s a social issue’, has found that there is a stark health inequality between men and women when it comes to suicide. Men were 3 times more likely than women to end their lives by suicide. Socio economic factors also increased suicide risk with those from the lowest social class, living in the most deprived areas, and the unemployed being at notably higher risk.

75% of people affected by hepatitis C in Scotland are in the lowest 2 quintiles of deprivation. These pieces of research reinforce that policies which may further entrench poverty or deprivation are likely to increase negative health outcomes.

To view presentations from a recent event discussing this research, including contributions from the Scottish Government, Choose Life and the Mental Health Foundation, click here.

Researchers uncover Hepatitis C infection method

US researchers have improved understanding of how the Hepatitis C virus infects cells. The research (HCV IRES manipulates the ribosome to promote the switch from translation initiation to elongation) could help to improve to improve treatment for patients in the future.

Research had previously established that the virus affects riboneucleic acid (RNA) which helps cells to produce proteins. The Hepatitis C virus essentially takes control of this process and forces cells to produce proteins vital to its’ own survival and multiplication.

The researchers were able to identify how the Hepatitis C virus takes over this process and found that they could easily block it from happening – therefore acting as a potential treatment method.

Hepatitis C Treatment updates:

Research into the Eligibility and Safety of Triple Therapy for Hepatitis C

This research considers the safety and eligibility profile for treatment with Protease Inhibitors in a real world setting. Whilst the addition of Protease Inhibitors to standard of care treatment has been shown to boost SVR rates significantly, several adverse treatment responses have been noted. This research also points out that original clinical trials reporting SVR rates of up to 80% were selective as patients with advanced liver disease and co-morbidities were under-represented or entirely excluded. Subsequent French research showed that in those with advanced liver fibrosis, many people experienced severe adverse effects from treatment. Contraindications may also pose a problem for eligibility due to triple therapy with Protease Inhibitors being based on treatment with Interferon alfa.

This research looks at triple therapy in the real world setting of a German referral centre.

For predicting SVR (sustained viral response or clearance), Hepatitis C genotype, stages of liver fibrosis, baseline viral load and age were already known predictors. Recently interleuckin-28B polymorphism genotypes were also found to be predictors of SVR in CHC (Chronic Hepatitis C) genotype 1 patients but not in CHC genotype 2 patients. This piece of research, published in the Annals of Hepatology, looked to further our understanding of age as a predictor for SVR and how this related to interleukin-28B.

Flu can Fly, no cough or sneeze

The influenza virus can spread up to 6 feet from a patient's head via submicron particles during routine hospital care, according to a study of patients admitted with influenza-like illness during the 2010 to 2011 influenza season

Although the anti-hepatitis C virus effects of statins in vitro and clinical efficacy of fluvastatin have been reported, the details of clinical presentation are largely unknown. This piece of research focused on viral relapse influencing treatment outcomes.

Advanced stage liver fibrosis in hepatitis C patients is associated with failure of interferon treatment and progression to more serious liver complications such as cirrhosis and liver cancer. As such the assessment of liver fibrosis is extremely important in clinical practice. Liver biopsy is the best way to measure liver fibrosis, however, the procedure is invasive and problems with sampling errors have been noted.

This study aimed to investigate the utility of real time assessment of the FIB-4 index in predicting progression of liver fibrosis. It concludes that the FIB-4 index is indeed useful for real time estimation of progression of liver fibrosis, while acknowledging that liver biopsy remains the gold standard for estimating liver fibrosis.

However, due to the invasiveness of liver biopsy procedures – meaning that they cannot be performed regularly enough to observe time course changes in liver fibrosis – the study authors recommend using biopsy to determine the baseline of fibrosis stage along with the serial measurement of the FIB-4 index to predict changes of fibrosis stages over time in a real time manner.

Hepatitis C drug updates

Boehringer Ingelheim has begun recruitment of patients for a phase 3 clinical trial of its’ investigational therapy regimen combining a once daily dose of protease inhibitor Faldaprevir and non nucleoside polymerase inhibitor BI 207 127 Plus along with Ribavirin. The study aims to highlight the benefits of alternatives to treatment with interferon and is part of a race to all oral interferon free treatments by various drug companies.

Gilead Sciences have announced results from phase 3 trials of their oral treatment Sofosbuvir in combination with Ribavirin and in combination with peginterferon and ribavirin. The studies showed that Sofosbuvir combined with peginterferon and ribavirin achieved the best results with 97% achieving SVR. However, Sofosbuvir combined with only ribavirin achieved SVR in the same percentage of cases (67%) as treatment with standard of care therapy.

Meanwhile, Idenix pharmaceuticals have dropped 2 experimental Hepatitis C drugs. The drugs had been placed on hold by the US Food and Drug Administration after serious safety concerns caused testing of a similar drug produced by Bristol Meyers Squibb to be halted.

Hepatitis B updates

Court overturns Hepatitis B patent

A US Federal court has declared invalid a patent on Bristol Myers Squibb’s Hepatitis B drug Baraclude following a challenge by generic drug maker Teva Pharmaceuticals.

Bristol Myers Squibb are currently considering whether to appeal the decision and it is as yet unclear whether US regulators will allow the generic form of Baraclude onto the market before the chemical patent on Baraclude lapses in 2015.

Research published in the Journal of Clinical Investigation which suggests that activation of a specific miRNA or inhibition of HPIP – a protein which regulates cancer cell growth – may be a useful strategy for HBV related cancer treatment.

Positive HBV Surface antigen tests can be due to recent vaccination

A retrospective study seeking to clarify the frequency and duration of transient HBsAG positivity following HBV vaccination. The study confirmed that transient HBsAG positivity can occur in patients following vaccination, but it is unlikely to persist beyond 14 days post vaccination. The study also demonstrated that weak positivity results do not reflect actual HBV infection, highlighting the importance of confirmatory testing.